A bacterial pigment provides cross-species protection from HO- and neutrophil-mediated killing.

Bacterial infections are often polymicrobial. and cause chronic co-infections, which are more problematic than mono-species infections. Understanding the mechanisms of their interactions is crucial for treating co-infections. Staphyloxanthin (STX), a yellow pigment synthesized by the operon, promotes resistance to oxidative stress and neutrophil-mediated killing. We found that STX production by , either as surface-grown macrocolonies or planktonic cultures, was elevated when exposed to the exoproduct, 2-heptyl-4-hydroxyquinoline N-oxide (HQNO). This was observed with both mucoid and non-mucoid strains. The induction phenotype was found in a majority of and clinical isolates examined. When subjected to hydrogen peroxide or human neutrophils, survival was significantly higher when mixed with wild-type (WT) , compared to alone or with an mutant deficient in STX production. In a murine wound model, co-infection with WT , but not the STX-deficient mutant, enhanced burden and disease compared to mono-infection. In conclusion, we identified a role for HQNO mediating polymicrobial interactions with by inducing STX production, which consequently promotes resistance to the innate immune effectors HO and neutrophils. These results further our understanding of how different bacterial species cooperatively cause co-infections.